Tigemonam's in vitro activity was compared with that of aztreonam, cefotaxime, gentamicin, and norfloxacin. Thirty-two strains of Pseudomonas and 960 strains of Enterobacteriaceae were studied using the agar dilution method (including Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter sp., Serratia marcescens, Proteus mirabilis, Proteus vulgaris, Morganella morganii, and Salmonella enterica). Tigemonam displayed good activity against Enterobacteriaceae. Minimum inhibitory concentrations (MICs), were as follows: MIC50S were 0.01 mg/L for P. mirabilis and 0.5 mg/L for S. marcescens, MIC90S were 0.03 mg/L for P. mirabilis and P. vulgaris and 4 mg/L for Citrobacter freundii. Tigemonam inhibited E. coli and P. mirabilis, the most common strains of urinary pathogens. Despite MIC90S of 9.5 and 4 mg/L for Enterobacter and C. freundii, respectively, resistance to tigemonam was observed. Tigemonam was found to be inactive against Pseudomonas aeruginosa, with MIC50S and MIC90S higher than 128 mg/L (range, 64 to greater than 128 mg/L). Tigemonam's activity was found to be similar to that of cefotaxime, slightly less than that of norfloxacin and aztreonam, and substantially greater than that of gentamicin. Of all the drugs tested, only norfloxacin and aztreonam possessed activity profiles against P. aeruginosa that were compatible with their clinical usefulness (MIC90, 8 mg/L for norfloxacin; MIC50, 8 mg/L and MIC90, 32 mg/L for aztreonam). Cefotaxime and gentamicin showed no activity on more than 90% of the P. aeruginosa strains tested.